US3300522A - Process for the preparation of 17alpha-hydroxy-16, 20-diketo pregnanes - Google Patents
Process for the preparation of 17alpha-hydroxy-16, 20-diketo pregnanes Download PDFInfo
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- US3300522A US3300522A US443669A US44366965A US3300522A US 3300522 A US3300522 A US 3300522A US 443669 A US443669 A US 443669A US 44366965 A US44366965 A US 44366965A US 3300522 A US3300522 A US 3300522A
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- hydroxy
- keto
- diketo
- steroid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Definitions
- This invention relates to a new chemical process for preparing 17a-hydroxy-16,20diket'o steroids.
- the process of this invention essentially comprises reacting a 16,20-diketo steroid of the pregnane (including the pregne-ne, pregnadiene and pregnatriene series), unsubstituted in the 17-.p0sition, With a peracid.
- suit-able peracids may be mentioned hydrogen peroxide and organic peracids, such as perbenzoic acid, haloperbenzoic acids (e.g., m-chloroperbenzoic 'acid), (lower alkyl)perbenzoic acids (e.g., pertoluic acid), pertlialic acid, and per(lower alkanoic) acids (e.g., penacetic acid).
- perbenzoic acid haloperbenzoic acids
- lower alkyl)perbenzoic acids e.g., pertoluic acid
- pertlialic acid e.g., per(lower alkanoic) acids
- penacetic acid per(lower alkanoic) acids
- the reaction is carried out under normal conditions, such as ambient temperature and pressure, preferably in the presence of an organic solvent for the steroid reactant.
- Suitable stenoid substrates are all steroids of the pregnane series that are unsubstituted in the 17- position and contain keto groups in at least the 16 and 20 positions.
- steroids include lfi-ketoprogesterone,
- 9u-h a1o-16-ketocorticosterones and 21-esters thereof such as 9ot-fluoro-16-ketocorticosterone and its 21- acet-ate 9a-halo-16-keto-1-dehydrocorticostenones and 2 l-esters thereof (such as 9a-fluo-ro-l6-keto-1rlehydrocorticos-terone and its 2l-acet-ate) 9a-halo-16-keto-6-dehydrocorticosterones and 21- esters thereof,
- the products obtained correspond to the steroid reactant but contain a 17a-hydroxy group.
- 16-ketoprogesterone as the reactant
- 16-ket'o 17a-hydroxyprogesterone a steroid having progestational activity
- the other 17a-hy drox steroids formed possess gluoocorticoid activity if they contain a llfl-hydroxy or ll-keto group, and progestational activity if there is no substitution in the C-ring.
- EXAMPLE 2 1 6-ket0-1 7 a-hydroxy-A -n0rpr0gester0ne
- any other 17-unsubstituted 16,20-diketo steroid of the pregnane series may be substituted for th l6-ketoprogesterone in the procedure of Example 1 t( yield the corresponding 17u-hydroxy-16,20-diketo derivative as the product obtained.
- a process for preparin a 17a-hyd-roxy-16,20-diketo steroid of the pregnane series which comprises intenacting a l7-unsubstituted 16,20-diketo steroid of the preg same series with a penacid.
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- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
United States Patent 3,300,522 PROCESS FOR THE PREPARATION OF 170t- HYDROXY-16,20-DIKETO PREGNANES Patrick A. Diassi, Westfield, N.J., assignor, by mesne assignments, to E. R. Squibb & Sons, Inc., New York,
N.Y., a corporation of Delaware No Drawing. Filed Mar. 29, 1965, Ser. No. 443,669
5 Claims. (Cl. 260397.4)
This invention relates to a new chemical process for preparing 17a-hydroxy-16,20diket'o steroids.
The process of this invention essentially comprises reacting a 16,20-diketo steroid of the pregnane (including the pregne-ne, pregnadiene and pregnatriene series), unsubstituted in the 17-.p0sition, With a peracid.
Among the suit-able peracids may be mentioned hydrogen peroxide and organic peracids, such as perbenzoic acid, haloperbenzoic acids (e.g., m-chloroperbenzoic 'acid), (lower alkyl)perbenzoic acids (e.g., pertoluic acid), pertlialic acid, and per(lower alkanoic) acids (e.g., penacetic acid). Although the proportion of peracid to steroid reactant is not critical, preferably at least about 1 mole of peracid is present per mole of steroid, and optimally about 1 to about 3 moles of peracid per mole of steroid is used. The reaction is carried out under normal conditions, such as ambient temperature and pressure, preferably in the presence of an organic solvent for the steroid reactant.
Among the suitable stenoid substrates are all steroids of the pregnane series that are unsubstituted in the 17- position and contain keto groups in at least the 16 and 20 positions. Such steroids include lfi-ketoprogesterone,
l6-keto-A-norp-rogesterone,
1 6-ketol dehyd-ropriogesterone,
16-keto-6-dehydroprogesterone,
16-ket-o-1l-desoxyco rticosterone and 21-esters thereof,
1 6-keto-1,6-tetrahydroprogesterone,
16-ketopregnenol-one,
6ot-methyl-16-ketoprogesterone,
16B-chloro-16-ketoprogesterone,
6ot-fluoro- 1 6-ketoprogeste none,
9cx-h'2li0-1 lfl-hydroxy-l 6-ket-oprogesterones (such as 900-- fiuoro- 1 lfl-hydroxy-l 6-ketoprogesterone) 9oc-h alo- 1 1, 16-diketoprogeste=rone-s,
9a-halo-1 1 [i-hydroxy- 1 6-ketol-dehydnoproge-sterones,
9oc-h'alO-1 l fi-hydroxy- 1 6-keto-6-'dehydroprogesterones,
60,9oc-dih3lO-1 1,B-hydroxy-l6-ketop rogesterones,
9u-h a1o-16-ketocorticosterones and 21-esters thereof (such as 9ot-fluoro-16-ketocorticosterone and its 21- acet-ate 9a-halo-16-keto-1-dehydrocorticostenones and 2 l-esters thereof (such as 9a-fluo-ro-l6-keto-1rlehydrocorticos-terone and its 2l-acet-ate) 9a-halo-16-keto-6-dehydrocorticosterones and 21- esters thereof,
90L,21-dih3.10-1 lfl-hpdroxy- 1 6-ketoprogesterones,
9a-21-dihalo-1 1B-hydroxy-1 6-keto-1-dehydr'op1'ogesterones,
9a,21-d1i'hal=o- 1 lB-hydr0xy-16-ketofi-dehydropnogesterones,
9a-halo-1 1 ,811ydnoxy-16-keto-A-norprogesterones,
16-keto-l9-norprogesterone,
1 6-keto-1 9-norcortiooster one,
6a-halo-1 lfi-hydroxy-16-ketocorticosterones and their 2 1 esters,
and 6a-halo-1 1 -p-hy-droxy- 1 6-keto- 1-dehydnocorticosterones and their 21-esters.
The products obtained correspond to the steroid reactant but contain a 17a-hydroxy group. Thus, for example, by employing 16-ketoprogesterone as the reactant,
ice
16-ket'o 17a-hydroxyprogesterone, a steroid having progestational activity, is obtained. The other 17a-hy drox steroids formed possess gluoocorticoid activity if they contain a llfl-hydroxy or ll-keto group, and progestational activity if there is no substitution in the C-ring.
The following examples illustrate the invention:
EXAMPLE 1 1 6-ket0-1 7 a-hydroxyprogesterone To a solution of 215 mg. (0.65 mmol) of 16-ketoprogesterone in 4 ml. of chloroform are added 15 0 mg. 0: m-chloroperbenzoic acid and the resulting solution lef at room temperature for two hours. It is then dilute with 20 ml. of chloroform and Washed with an equa volume of 5% sodium bicarbonate followed by water The organic phase is then dried over sodium sulfate ant evaporated to dryness in vacuo. Crystallization of th residue from acetone-hexane gives about 158 mg. of 16 keto-l7ot-hydnoxyprogesterone having a melting poin= about 205-207 C., [04 90.7 (chloroform),
x313, 239 mn(e, 18,700 x3 3? 3550, 3450, 1756, 1708 1681 emf, T239 1 4.25 (s., 4H), 7.73 (S., 21Me) 8.98 (s., 19Me), 9.01 (s., 18Me).
Analysis.Calod. for C H O (344.44): C, 73.22 H, 8.19. Found: C, 72.99; H, 8.24.
EXAMPLE 2 1 6-ket0-1 7 a-hydroxy-A -n0rpr0gester0ne (a) Preparation of A-n0rpregn-3-en-2,16,20-tri0ne. To a solution of 600 mg. of 16u-hydroxy-A-norproges terone in 150 ml. of reagent grade acetone, 8 ml. of a1 acetone-water (9:1, vzv) solution containing 20 mg. 0 01-0 and 32 mg. of sulfuric acid per milliliter are adder dropwise with stirring. After 10 minutes a few drop: of methanol are added, the mixture diluted with Wate: and partially evaporated in vacuo. It is then extracte( with chloroform which is washed with water, dried o-ve: sodium sulfate and evaporated to dryness. Cryst'alliza tion of the residue from acetone-hexane or ether give: about 400 mg. of A-norpregn-3-en-2,16,20-trione having melting .point of about 128-130 C.
(11) Preparation of 16-ket0-17a-hydroxy-A-norproges ter0ne.T-o a solution of 157 mg. (0.5 mmol) of 16 keto-A-norprogestenone in 4 ml. of chloroform are adder mg. of m-chloroperbenzoic acid and the resulting solution kept at room temperature for two hours. Fol lowing the procedure of Example 1 there is obtaine about 98 mg. of l6-keto-l7a-hydroxy-A-norprogesteroni having a melting point about 218220 C.,
mg, 232 mp. (6, 19,800) 51 -197 (chloroform), 2.98, 5.70, 5.89, 6.18 7, ,3 5? 4.23 (s., on), 7.7: (s, 21Me), 8.78 (3., 19Me), 9.03 (s., 18-Me).
Analysis.Calcd. for 0201 12 0}; C, H, 7.93. Found: C, 72.77; H, 7.79.
Similarly, any other 17-unsubstituted 16,20-diketo steroid of the pregnane series may be substituted for th l6-ketoprogesterone in the procedure of Example 1 t( yield the corresponding 17u-hydroxy-16,20-diketo derivative as the product obtained.
Moreover, if any other per-acid is substituted for the m-chloroperbenzoic acid in the procedures of either Example 1 or 2, the same product is obtained.
The invention may be variously otherwise embodied within the scope of the appended claims.
What is claimed is:
1. A process for preparin a 17a-hyd-roxy-16,20-diketo steroid of the pregnane series which comprises intenacting a l7-unsubstituted 16,20-diketo steroid of the preg same series with a penacid.
2. The process of claim 1 wherein the peracid is an organic peracid.
3. The process of claim 1 wherein the peracid is mchloroperbenzoic acid.-
4. The process of claim 1 wherein the steroid is 16- ketoprogesterone.
5. The process of claim 1 wherein the steroid is 16- keto-A-norprogesterone.
No references cited.
ELBERT L. ROBERTS, Primary Examiner.
Claims (1)
1. A PROCESS FOR PREPARING A 17A-HYDROXY-16,20-DIKETO STEROIDS OF THE PREGNANE SERIES WHICH COMPRISES INTERACTING A 17-UNSUBSTITTUED 16,20-DIKETO STEROID OF THE PREGNANE SERIES WITH A PERACID.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US443669A US3300522A (en) | 1965-03-29 | 1965-03-29 | Process for the preparation of 17alpha-hydroxy-16, 20-diketo pregnanes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US443669A US3300522A (en) | 1965-03-29 | 1965-03-29 | Process for the preparation of 17alpha-hydroxy-16, 20-diketo pregnanes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3300522A true US3300522A (en) | 1967-01-24 |
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ID=23761743
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US443669A Expired - Lifetime US3300522A (en) | 1965-03-29 | 1965-03-29 | Process for the preparation of 17alpha-hydroxy-16, 20-diketo pregnanes |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3300522A (en) |
-
1965
- 1965-03-29 US US443669A patent/US3300522A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
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